Unexpected mexiletine responses of a mutant cardiac Na+ channel implicate the selectivity filter as a structural determinant of antiarrhythmic drug access
K Sasaki, N Makita, A Sunami, H Sakurada… - Molecular …, 2004 - Elsevier
Gating properties of Na+ channels are the critical determinants for the state-dependent block
by class I antiarrhythmic drugs; however, recent site-directed mutagenesis studies have
shown that the Na+ channel selectivity filter region controls drug access to and dissociation
from the binding site. To validate these observations, we have exploited a naturally
occurring cardiac Na+ channel mutation, S1710L, located next to the putative selectivity filter
residue of domain 4, and evaluated the pharmacological properties to mexiletine using …
by class I antiarrhythmic drugs; however, recent site-directed mutagenesis studies have
shown that the Na+ channel selectivity filter region controls drug access to and dissociation
from the binding site. To validate these observations, we have exploited a naturally
occurring cardiac Na+ channel mutation, S1710L, located next to the putative selectivity filter
residue of domain 4, and evaluated the pharmacological properties to mexiletine using …